Transfer RNA Genes Affect Chromosome Structure and Function via Local Effects

Abstract

The genome is packaged and organized in an ordered, non-random manner and specific chromatin segments contact nuclear substructures to mediate this organization. While transfer RNA genes (tDNAs) are essential for the generation of tRNAs, these loci are also binding sites for transcription factors and architectural proteins and are thought to play an important role in the organization of the genome. In this study, we investigate the role of tDNAs in genomic organization and chromosome function by editing a chromosome so that it lacks any tDNAs. Surprisingly our analyses of this tDNA-less chromosome show that loss of tDNAs does not grossly affect chromosome folding or chromosome tethering. However, loss of tDNAs affects local nucleosome positioning and the binding of SMC proteins at these loci. The absence of tDNAs also leads to changes in centromere clustering and a reduction in the frequency of long range HML-HMR heterochromatin clustering. We propose that the tDNAs primarily affect local chromatin structure that result in effects on long-range chromosome architecture.

Distinct silencer states determine epigenetic states of heterochromatin

“…Alternatively, it is possible that both alleles of HMRα could affect each other through a process similar to transvection, in which physical proximity of two alleles allows them to be co-regulated. This possibility would be consistent with observations that silenced loci can physically interact in the nucleus (Hamdani et al, 2019; Miele et al, 2009).…”